HQ Team
February 24, 2025: Mirum Pharmaceuticals Inc.’s oral cholesterol drug for treating a rare metabolic disease has been approved by the Food and Drug Administration.
The FDA approved the California-based company’s Ctexli (chenodiol) for cerebrotendinous xanthomatosis in adult patients, the first such approval for the disorder from the drug regulator, according to a statement.
The FDA granted Ctexli Priority Review, Fast Track and Orphan Drug designations for this application.
Cerebrotendinous xanthomatosis is a genetic metabolic disorder caused by a mutation in a gene resulting in a deficiency of the enzyme important in the body’s ability to break down fats.
Deposition of metabolites
Due to reduced bile acid production in the liver, patients with the disorder won’t be able to break down cholesterol normally.
This results in the deposition of atypical cholesterol metabolites (substances that result from the breakdown of cholesterol) in various places in the body including the brain, liver, skin and tendons, leading to damage to those organs and tissues.
Ctexli works to replace deficient levels of one of the bile acids, reducing the abnormal deposits of cholesterol metabolites thought to be responsible for clinical abnormalities in the disorder.
Rare diseases
“The FDA is dedicated to supporting new drug development for rare diseases including very rare metabolic diseases like cerebrotendinous xanthomatosis,” said Janet Maynard, MD, MHS, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research.
“Cerebrotendinous xanthomatosis (CTX) is a progressive multisystemic disorder that significantly impacts patients and previously lacked approved treatments. Today’s approval provides a safe and effective treatment option,” the disorder, she said.
The efficacy of Ctexli in patients with CTX was evaluated in a double-blind, placebo-controlled, randomized crossover withdrawal trial, according to the FDA.
The 24-week trial demonstrated that treatment with Ctexli, 250 milligrams three times per day, showed a significant reduction in plasma cholestanol and urine 23S-pentol compared to placebo treatment.
Diarrhoea, muscular weakness
Plasma cholestanol is a measurement of the level of cholestanol in the blood. Cholestanol is a derivative of cholesterol that is involved in the synthesis of bile acids.
The prescribing information for Ctexli includes a warning for liver toxicity in all patients with increased risk for liver damage in patients with pre-existing liver disease or bile duct abnormalities, according to the FDA statement.
The most common side effects of Ctexli are diarrhoea, headache, abdominal pain, constipation, hypertension, muscular weakness and upper respiratory tract infection.
The recommended dosage is 250 milligrams, taken orally three times a day.
